Glucosamine is a substance
synthesized in the body.It plays an important role in the repair and
maintenance of Articular cartilage

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Glucosamine sulfate is an
artificially synthesized salt of glucsamine. This compound has been used
for many years as a natural treatment for arthritis and in particular, osteoarthritis.

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Osteoarthritis is a form of degenerative
arthritis occurring when the cartilage that cushions the ends of bone joints breaks down,
causing pain, stiffness and deformity.

In animal models of arthritis, glucosamine sulfate
was reported to have the potential to slow the degradation of cartilage. Its mode of action is believed to involve stimulation of
cartilage cells to synthesize the building blocks of cartilage - called glycosaminoglycans and proteoglycans. It also has been reported to have anti-inflammatory properties through a
mechanism that inhibits the activity of proteolytic enzymes.
In the early 1980s, a number of small, controlled human
trials were conducted in Europe and Asia to study the clinical use of glucosamine sulfate
in the treatment of osteoarthritis.

Small trials were then done in the early
1990's. These studies all showed that glucosamine sulphate had a
benefit when used as a sulphate.

Chloride did not help. Glucosamine
chloride was tested in a large study by the USA National institutre of
health and again confirmed that Glucosamine Chloride does
not work.

However early and more recent
studies show that Glucosamine SULPHATE works.

Therefore in my personal opinion
there is fairly good evidence that there is benefit in osteoarthritis.

I
have therefore prescribed it for many years.

Use in other Arthritis
types such as Rheumatoid arthritis has not been fully tested, but there is
certainly no harm in using it as a cartilage protector.

Publication in the
Lancet Vol 357 Jan 2001 showed optimistic results with an increase in joint
space (cartilage) when used over 3 years.

This suggests a fairly
definite positive response

Efficacy and Safety of
Glucosamine SULFATE IN OSTEOARTHRITIS OF THE SPINE: A PLACEBO-CONTROLLED,
RANDOMISED, DOUBLE-BLIND STUDY

Objective: Control of
symptoms of cervical and/or lumbar spondylarthrosis in comparison with
placeboSix weeks of treatment plus four weeks of follow-up. 160
patients were enrolled, randomly assigned to either the verum group (80
patients: 66 women, 14 men; mean age of 64.2 years) or to the placebo group
(80 patients: 65 women, 15 men; mean age of 62.0 years).

Global assessment, figures
were higher: 67.5 versus 58.8% (not significant, n.s.). Conclusions:
GS has a significantly better symptomatic efficacy than placebo in
controlling pain and movement limitation in spondylarthrosis. This effect
lasts on after the end of treatment, whereby safety of GS is very good and
comparable to that of placebo.

GLUCOSAMINE SULPHATE IN OSTEOARTHRITIS: A SYSTEMATIC
REVIEW

T.E. Towheed

Rheumatic Diseases Unit, Queen's University, Canada

Glucosamine sulphate (GS) has been proposed as a slow acting drug in
osteoarthritis (OA). Randomized controlled trials (RCTs) evaluating the efficacy of GS in
the management of OA were systematically reviewed. A MEDLINE search strategy, supplemented
by a review of reference lists, was used to help identify English language RCTs published
between 1966 and 1997. Quantitative review of the efficacy of GS in OA was performed by
meta-analysis. Effect sizes were used to synthesize quantitative data that were measured
with different scales, and P Odds Ratios (OR) were used for pooling dichotomous data.
The search strategy identified a total of 9 RCTs. The average duration of the RCTs was 5.4
weeks. The mean number of subjects randomized subjects was 97. GS was administered orally
in 5 RCTs, parenterally in 2, and a combined oral/parenteral route was used in 2 RCTs. 6
RCTs included subjects with only OA of the knee, 2 did not state the location of the OA,
and 1 included subjects with OA at multiple sites. In the 7 RCTs that compared GS versus
placebo, GS was always superior. 2 RCTs: compared GS versus ibuprofen;GS was superior in 1
and equivalent in 1. There were methodological problems with these RCTs, including a lack
of standardization of the case definition of OA, and a lack of standardization of outcome
assessment. The combined effect size for pain relief, comparing GS vs placebo (n = 5
studies) was 1.23 (95% CI, .93 to 1.53). The P OR, for overall favorable response
comparing GS versus placebo (n = 2 studies) was 2.04 (95% CI, 1.38 to 3.02).

GS was found
to be extremely safe and superior to placebo, and at least similar in efficacy to
ibuprofen. Further studies are needed to determine whether the route of administration of
GS is clinically important, and whether the therapeutic effect of GS in OA is site
specific.

INTRODUCTION: A total of 177 patients
with moderate-to-severe hip or knee osteoarthritis (OA) were tested over a
period of 26 weeks in a two-center, two-armed, randomized, double-blind,
comparison study.

The aim was to see if a combination of glucosamine sulfate (1500
mg/day) and the omega-3 polyunsaturated fatty acids eicosapentaenoic acid
(EPA) and docosahexaenoic acid (DHA) (group A), showed equivalence (noninferiority)
or superiority as opposed to glucosamine sulfate alone (group B).

METHODS: The primary therapy evaluation was performed using the Western
Ontario and McMaster Universities Arthrosis index (WOMAC) score. At the
end of the study, a reduction in the pain score of > or =20% was required
(primary target criterion) and the quantitative difference in the WOMAC
subscores pain, stiffness, and function were analyzed (secondary target
criteria).

RESULTS AND CONCLUSION: When a minimal pain reduction of > or =20% was
chosen, there was no statistically significant difference in the number of
responders between the two groups (92.2% group A, 94.3% group B). A higher
responder criterion (> or =80% reduction in the WOMAC pain score) was
chosen. Therefore, the frequency of responders showed a therapeutic and
statistical superiority for the combination product of glucosamine sulfate
and the omega-3 polyunsaturated fatty acids in patients who complied with
the study protocol (group A 44%, group B 32%; P=0.044).

OA symptoms (morning stiffness, pain in hips and knees) were reduced at
the end of the study: by 48.5%-55.6% in group A and by 41.7%-55.3% in
group B. The reduction was greater in group A than in group B.

There was a tendency toward superiority shown in the secondary target
criteria and concurrent variables. In the global safety evaluation, both
products have been demonstrated to be very safe in long-term treatment
over 26 weeks.

To our knowledge, this is the first clinical trial in which glucosamine
was given in combination with omega-3 fatty acids to patients with OA.

INTRODUCTION: The aim of this study was to explore the cost-effectiveness
of glucosamine sulphate (GS) compared with paracetamol and placebo (PBO)
in the treatment of knee osteoarthritis. For this purpose, a 6-month time
horizon and a health care perspective was used.

MATERIAL AND
METHODS: The cost and effectiveness data were derived from Western Ontario
and McMaster Universities Osteoarthritis Index data of the Glucosamine
Unum In Die (once-a-day) Efficacy trial study by Herrero-Beaumont et al.
Clinical effectiveness was converted into utility scores to allow for the
computation of cost per quality-adjusted life year (QALY) For the three
treatment arms Incremental Cost-Effectiveness Ratio were calculated and
statistical uncertainty was explored using a bootstrap simulation.
RESULTS: In terms of mean utility score at baseline, 3 and 6 months, no
statistically significant difference was observed between the three
groups. When considering the mean utility score changes from baseline to 3
and 6 months, no difference was observed in the first case but there was a
statistically significant difference from baseline to 6 months with a
p-value of 0.047.

When comparing GS with paracetamol, the mean
baseline incremental cost-effectiveness ratio (ICER) was dominant and the
mean ICER after bootstrapping was -1376 euro/QALY indicating dominance
(with 79% probability). When comparing GS with PBO, the mean baseline and
after bootstrapping ICER were 3617.47 and 4285 euro/QALY, respectively.

CONCLUSION: The results of the present cost-effectiveness analysis
suggested that GS is a highly cost-effective therapy alternative compared
with paracetamol and PBO to treat patients diagnosed with primary knee OA.

Rheumatol Int. 2010 Jan;30(3):357-63. Epub 2009 Jun
21.

Effect of glucosamine or chondroitin sulfate on the
osteoarthritis progression: a meta-analysis. Lee YH, Woo JH, Choi
SJ, Ji JD, Song GG. Division of Rheumatology, Department of Internal
Medicine, Korea University Anam Hospital, Korea University College of
Medicine

The aim of this study was to assess the structural
efficacies of daily glucosamine sulfate and chondroitin sulfate in
patients with knee osteoarthritis (OA). The authors surveyed randomized
controlled studies that examined the effects of long-term daily
glucosamine sulfate and chondroitin sulfate on joint space narrowing (JSN)
in knee OA patients using the Medline and the Cochrane Controlled Trials
Register, and by performing manual searches.

Meta-analysis was
performed using a fixed effect model because no between-study
heterogeneity was evident. Six studies involving 1,502 cases were included
in this meta-analysis, which consisted of two studies on glucosamine
sulfate and four studies on chondroitin sulfate. Glucosamine sulfate did
not show a significant effect versus controls on minimum JSN over the
first year of treatment (SMD 0.078, 95% CI -0.116 to -0.273, P = 0.429).
However, after 3 years of treatment, glucosamine sulfate revealed a small
to moderate protective effect on minimum JSN (SMD 0.432, 95% CI
0.235-0.628, P < 0.001). The same was observed for chondroitin sulfate,
which had a small but significant protective effect on minimum JSN after 2
years (SMD 0.261, 95% CI 0.131-0.392, P < 0.001). This meta-analysis
of available data shows that glucosamine and chondroitin sulfate may delay
radiological progression of OA of the knee after daily administration for
over 2 or 3 years.

GLUCOSAMINE (GL) AND CHONDROITIN (CH) TREATMENT FOR OSTEOARTHRITIS (OA) OF THE
KNEE OR HIP: META-ANALYSIS AND QUALITY ASSESSMENT OF CLINICAL TRIALS

T.E. McAlindon, J. Gulin, D.T. Felson

Arthritis Ctr., Boston Univ., MA 02118, USA

OA is a major cause of pain and disability in the population for which effective
treatment is badly needed. GL and CH have been used for over 10 years in Europe, yet have
been neglected as credible OA therapies in the US. Because of their safety, GL and CH
would be of value even if only modestly effective. We performed a meta-analysis and
quality assessment of clinical trials to evaluate their efficacy, and the quality of the
evidence.

Studies eligible for inclusion were double-blind placebo-controlled trials of
³4 weeks duration, testing oral or
parenteral GL or CH for knee or hip OA, which reported p values and size of
treatment effect. Studies were sought using MEDLINE, manual searches of manuscripts and
journal supplements, and by contacting authors of published manuscripts and content
experts. Study quality was scored independently by two observers using a validated
inventory with range 0-65, in which scores £ 33 are considered poor, 34-45 moderate,
³46 good (JAMA 1994; 272: 108). Disagreements were treated by adjudication, and by
taking averages.

We decided a priori to (i) treat the global pain score in the index joint (or, if
unavailable, the Lequesne Index) as the study 1° outcome (ii) classify a trial as
positive if the score in the treated group at completion was ³25% lower than the placebo group and significant [p <
.05]. We then computed the probability that the observed number of positive studies might
have occurred by chance if the treatments were in fact ineffective using the sign test,
and the number of negative studies which would be required to make this result null (p
» .5).

Clinical trials of GL and CH show
substantial benefits in the treatment of OA, but provide insufficient
information about study design and conduct to allow definitive
evaluation. We conclude that further studies are needed to test the efficacy of GS and CS.